University Of Califoria, San Francisco
School of Medicine
Please address reply to the undersigned at:
San Francisco General Hospital
995 Potrero Avenue
Building 80, Ward 84
San Francisco, California 94110

April 28, 1995

Alan I. Leshner, Ph.D
National Institute on Drug Abuse
5600 Fishers Lane
Rockville, Maryland 20857

Dear Dr. Leshner,

I am writing in response to your letter of April 19 regarding my 
request that NIDA consider supplying marijuana for the Community 
Consortium's proposed study in patients with HIV-related wasting 
syndrome.  I was not only disappointed by the flat out rejection of 
the request, but also by the way this matter has been handled by your 
Institute from the onset.  To receive the first communication from 
your office nine months after we sent the initial submission is 
offensive and insulting.  I realize that this has been a very 
difficult decision for you to make because of all the nonscientific 
issues involved, but I am certainly not used to having no 
communication at all for nine months from someone with whom I had 
corresponded on an official matter.  The apparent abscence of any 
possibility to discuss your concerns and to modify the protocol 
appropriately so that we may work together for the benefit of our 
patients is also unacceptable in my opinion. 

The National Institute on Drug Abuse has not been the first body to 
review our proposed pilot study.  It has been reviewed and approved 
by the Committee on Human Research of the University of California, 
San Francisco, as well as by our own Scientific Advisory Committee 
and Community Advisory Forum.  In addition, the study has been 
approved (pending location of the source of inhaled marijuana) by the 
California Research Advisory Panel.  The US Food and Drug 
Administration has also been involved since the onset in developing 
the trial and has strongly influenced the study's design.  The 
General Clinical Research Center at San Francisco General Hospital 
has agreed to collaborate in the study by providing dietary 
counseling and monitoring of patients, as well as performing the 
state-of-the-art composition measurements we intend to perform. 
Collaborating investigators at Chiron Corporation were also eager to
participate in this study by donating their newly developed 
technology to assess HIV viral burden in patients randomized to 
receive marijuana.  Hence, your concerns about the scientific merit 
of the study have not been shared by a number of competent reviewers 
and investigators.

To respond to your concerns in a timely manner, I will address each 
issue you raise in turn.  However, it is important to stress that 
this trial was designed as a pilot study to determine the feasibility 
of conducting a larger study and, in particular, the sample size 
required to evaluate the efficacy of inhaled marijuana.  As you know, 
the use of a pilot study in clinical research is a well-established 
procedure.  I am sure you would agree that it is a prudent strategy 
to conduct a small pilot trial of inhaled marijuana prior to launching
the definitive efficacy trial that would require a much larger sample 

We fully appreciate that the current pilot study would not be 
adequate to "make any inferences regarding the dose-effect 
relationship."  However, we would be able to determine whether a dose 
was associated with an intolerable rate of side effects, and that 
dose would then be eliminated from a larger efficacy trial.  As 
indicated in the protocol, we plan to do intensive monitoring of 
pulmonary and immune function as well as HIV viral load in our 
patients.  If we saw that inhalation of marijuana was detrimental to 
any of these parameters, that information would be crucial to share 
with others in order to protect the safety of patients who are 
already using inhaled marijuana (from other sources).  The current 
pilot study certainly should be large enough (with 30 patients 
smoking marijuana) to assess such possible detrimental effects.

The Community Consortium conducts community-based clinical trials of 
treatments that are being widely used by the patient population and, 
as I am sure you are aware, individuals with access are currently 
utilizing inhaled marijuana.  Our aim is to assess the impact of 
treatments that we study in "real world" situations.  As you know, 
with whatever drug one studies in a clinical trial, we can never be 
truly certain that patients are consuming 100% of their assigned 
doses.  Even for treatment of Pneumococcal pneumonia, very few 
patients treated actually complete their full course of penicillin. 
Similarly, zidovudine (AZT) was approved as the first antiretroviral 
agent for treating HIV infectioin, and we know that compliance in 
those trials was not 100%.  In our study, we plan to ask patients to 
quantitate how much of their allotted marijuana they smoked on any 
given day.  We also plan to have patients return any unused marijuana 
so we can assess how much they actually usilized.  Whether they 
actually smoked all that they were given at each visit is irrelevant 
when an intent-to-treat analysis is utilized for data analysis.

Your concerns about total daily caloric intake and "the percentages 
of the composition of the foodstuffs" are a bit extreme, in my 
opinion, but do not present insurmountable problems for us.  As the 
General Clinical Research Center at San Francisco General Hospital is 
our collaborating site where patients will go to be taught how to use 
the water pipe for inhalation, and where they will return for all of 
their follow-up evaluations, obtaining this dietary information is 
certainly possible.  In fact, this is the sort of information that 
the GCRC specializes in collecting!  Though we could add this 
requirement, it would be a major inconvience to these already ill 
patients to ask them to collect this information on a daily basis 
during the trial.  Of course, another option is to admit all patients 
on the study to the GCR for the duration of their participation in 
the study, so that all intake and output can be accurately assessed. 
Once again, however, that is not how patients would be living while 
they utilized the intervention in the real world, so the value of 
data obtained in this fashion is, in my mind, unclear.  It certainly 
does not reflect the "real world" usage.

As an AIDS investigator who has worked closely with National 
Institutes of Health and the US Food and Drug Administration for the 
past 14 years of this epidemic, I must tell you that dealing with 
your Institute has been the worst experience of my career!  The lack 
of any official communication for nine months is unheard of, even in 
the most cumbersome of government bureaucracies.  In fact, I was so 
shocked to finally receive your communication that I failed to detach 
the green postcard to verify receipt.  I apologize to you, and to 
your staff who called for three consecutive days to make sure the 
letter had arrived.

Finally, the "sincerity" with which you share my "hope that new 
treatments will be found swiftly" feels so hypocritical that it makes 
me cringe.  Believe it or not, I wish I had never needed to approach 
NIDA with this request.  The Community Consortium had a source of 
marijuana established for this study from the onset.  Unfortunately, 
the source was foreign and the FDA advised us that the DEA was having 
difficulty with the importation issue and suggested we contact you. 
(The DEA has also been less than forthcoming in responding to my 
request for a Schedule I license sent to them April 15, 1994.)

Obviously, your letter leaves no door open for further discussion as 
to how this pilot study could be modified so that we could work 
together.  Hence, I will not bother you further.  Your letter will be 
widely distributed.  You had an opportunity to do a service to the 
community of people living with AIDS.  You and your Institute failed. 
In the words of the AIDS activist community: SHAME!



Donald I. Abrams, M.D.
Chairman, Community Consortium
Assistant Director, AIDS Program
San Francisco General Hospital
Professor of Clinical Medicine
University of California San Francisco

cc: Philip R. Lee, MD
    Harold E. Varmus, MD